Vascular Protective Effect of Rosuvastatin in Arteriovenous Fistula
Background Arteriovenous (AV) fistula is the most common vascular access for long-term hemodialysis in the end-stage renal disease (ESRD) patients. About 25% of these patients are diabetes mellitus. However, the effects of hyperglycemia on the vascular function of arteriovenous fistula are still remained unclear. Studies have shown that blood flow in the AV fistula is significantly reduced in patients with diabetes mellitus. Diabetic patients also require a longer period of time for the maturation of AV fistula, and have slightly higher complication rate than non-diabetic patients. Statins have been widely shown to mediate several important pleiotropic effects in the improvement of vascular endothelial dysfunction, attenuation of inflammatory responses, stabilization of atherosclerotic plaques, inhibition of vascular smooth muscle proliferation, and modulation of procoagulant activity and platelet function.Our experimental studies in diabetic animals demonstrate that administration of a water-soluble statin rosuvastatin significantly improves the fistula flow, vascular function and luminal dilatation of AV fistula in diabetic rats by suppression of vascular oxidative stress and inflammatory load.
Study hypothesis The central hypothesis of this research project is rosuvastatin mediates pleiotropic protective effect on vascular endothelial function and suppresses the regional pro-inflammatory reaction in the vasculature, therefore administration of rosuvastatin during the perioperative period of creation of native AV fistulas in diabetic patients with ESRD may potentiate the vascular function and reduce the primary failure rate of AV fistulae.
End-stage Kidney Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effect of Rosuvastatin in the Mobilization of Endothelial Progenitor Cells and Graft Vascular Function Following Creation of Arteriovenous Fistula in Diabetic Patients With Chronic Renal Failure|
- Primary patent rate of AV fistula [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]The definition of primary patency of an AV fistula is defined as successful cannulation of the fistula for first hemodialysis treatment (first dialysis session)(reference: BMC Nephrol 2013;14:79). Administration of rosuvastatin protects the endothelial function in the AV fistula and restores the blood flow rate in the shunt of diabetic patients with ESRD, thereby improves the primary patent rate and early maturation of these fistulas
- Composite outcome measurement of the overall shunt-related complication rate [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]The most commonly shunt-related complications are formation of aneurysms, failure of shunt to mature, and development of thrombosis in AV fistula (Ann Vasc Surg 2012;26:680). The occurrence of shunt-related complications usually require surgical reintervention. Administration of rosuvastatin improves the vascular function of AV fistulas in diabetic patients with ESRD, therefore reduces the overall shunt-related complication rate and the requirement for surgical re-interventions.
- Composite outcome measurement of systemic pro-inflammatory response [ Time Frame: 3 months after operation ] [ Designated as safety issue: No ]Systemic proinflammatory response is determined by measuring blood concentrations of MCP-1, IL-1 beta, IL-6 and TNF-alpha, and the numbers of circulating endothelial progenitor cells (EPCs). Administration of rosuvastatin is associated with reduction of the systemic pro-inflammatory response and oxidative stress (levels of proinflammatory cytokines and other mediators in the circulation) in diabetic patients with ESRD. On the other hand, administration of rosuvastatin may mobilize the bone marrow-derived EPCs into systemic circulation, and the number of these circulating endothelial progenitors may provide prognostic value to the outcomes of AV fistula.
|Study Start Date:||November 2012|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Placebo tablet contains only inactive ingredient. The placebo tablets will be taken once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Active Comparator: Rosuvastatin
Rosuvastatin (CrestorÒ, Astrazeneca) 5mg once daily for 4 weeks (1 week before operation and 3 weeks after creation of AV fistula)
Rosuvastatin tablet (CrestorÒ, Astrazeneca) 5 mg/d PO for 4 weeks (1 week before and 3 weeks after creation of AV fistula)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01863914
|National Cheng Kung University Hospital||Recruiting|
|Tainan, Taiwan, 704|
|Contact: Chen-Fuh Lam, MD, PhD 8866-2353535 ext 5348 email@example.com|
|Principal Investigator: Chen-Fuh Lam, MD, PhD|
|Sub-Investigator: Jun-Neng Roan, MD|